{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:48:09Z","timestamp":1788018489344,"version":"build-2784847793"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fujian Provincial Natural Science fund subject of China","award":["2022J01361"],"award-info":[{"award-number":["2022J01361"]}]},{"name":"Fujian Provincial Natural Science fund subject of China","award":["XJC2023004"],"award-info":[{"award-number":["XJC2023004"]}]},{"name":"Natural Science fund subject of Fujian University of traditional Chinese Medicine","award":["2022J01361"],"award-info":[{"award-number":["2022J01361"]}]},{"name":"Natural Science fund subject of Fujian University of traditional Chinese Medicine","award":["XJC2023004"],"award-info":[{"award-number":["XJC2023004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The development of BACE-1 (\u03b2-site amyloid precursor protein cleaving enzyme 1) inhibitors is a crucial focus in exploring early treatments for Alzheimer\u2019s disease (AD). Recently, graph neural networks (GNNs) have demonstrated significant advantages in predicting molecular activity. However, their reliance on graph structures alone often neglects explicit sequence-level semantic information. To address this limitation, we proposed a Graph and multi-level Sequence Fusion Learning (GSFL) model for predicting the molecular activity of BACE-1 inhibitors. Firstly, molecular graph structures generated from SMILES strings were encoded using GNNs with an atomic-level characteristic attention mechanism. Next, substrings at functional group, ion level, and atomic level substrings were extracted from SMILES strings and encoded using a BiLSTM\u2013Transformer framework equipped with a hierarchical attention mechanism. Finally, these features were fused to predict the activity of BACE-1 inhibitors. A dataset of 1548 compounds with BACE-1 activity measurements was curated from the ChEMBL database. In the classification experiment, the model achieved an accuracy of 0.941 on the training set and 0.877 on the test set. For the test set, it delivered a sensitivity of 0.852, a specificity of 0.894, a MCC of 0.744, an F1-score of 0.872, a PRC of 0.869, and an AUC of 0.915. Compared to traditional computer-aided drug design methods and other machine learning algorithms, the proposed model can effectively improve the accuracy of the molecular activity prediction of BACE-1 inhibitors and has a potential application value.<\/jats:p>","DOI":"10.3390\/ijms26041681","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T03:41:47Z","timestamp":1739763707000},"page":"1681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Graph and Multi-Level Sequence Fusion Learning for Predicting the Molecular Activity of BACE-1 Inhibitors"],"prefix":"10.3390","volume":"26","author":[{"given":"Shaohua","family":"Zheng","sequence":"first","affiliation":[{"name":"College of Physics and Information Engineering, Fuzhou University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwang","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Physics and Information Engineering, Fuzhou University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6430-2003","authenticated-orcid":false,"given":"Youjia","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Physics and Information Engineering, Fuzhou University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meimei","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1056\/NEJMe2103722","article-title":"Progress with Treatments for Alzheimer\u2019s Disease","volume":"384","author":"Levey","year":"2021","journal-title":"N. 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